Best of Best Poster Oral Clinical Oncology Society of Australia Annual Scientific Meeting 2019

NEU-HORIZONS: The neuroprotection and therapeutic use of riluzole for the prevention of oxaliplatin-induced neuropathy- a randomised controlled trial (#356)

Terry Trinh 1 , Susanna B Park 2 , Jenna E Murray 1 , Hannah Pickering 1 , Andrew Martin 3 , Michael L Friedlander 4 , Matthew C Kiernan 2 , David Goldstein 1 4 , Arun V Krishnan 5
  1. University of New South Wales, RANDWICK, NSW, Australia
  2. Brain and Mind Centre, University of Sydney, Camperdown, New South Wales, Australia
  3. NHMRC Clinical Trials Centre, University of Sydney, Camperdown, New South Wales, Australia
  4. Medical Oncology, Prince of Wales Hospital, RANDWICK, NSW, Australia
  5. Department of Neurology, Prince of Wales Hospital, RANDWICK, NSW, Australia

Aim

Peripheral neuropathy is a commonly reported adverse effect of oxaliplatin treatment, representing a significant limitation which may require discontinuation of effective therapy. The present study investigated the neuroprotective potential of riluzole, a drug currently used for the treatment of amyotrophic lateral sclerosis where it has demonstrated effective neuroprotection.

 

Methods

Fifty-two patients (17 females, 58.1±12.7 years) receiving oxaliplatin treatment were randomised into either a treatment (50 mg riluzole) or placebo group. The planned accrual was n=90 which was not met. The primary outcome measure was the Total Neuropathy Score-reduced (TNS-r). Secondary outcome measures include nerve excitability measures, 9-hole pegboard and FACT-GOG NTX questionnaire. The study drug/placebo was administered twice daily and ceased 2-weeks after the last cycle of treatment. Patients were assessed at baseline, pre-cycle 10 or 12, 4-weeks and 12-weeks post-treatment. A mixed-model of repeated measures modelling approach was implemented to account for the small sample size and missing data due to patient withdrawal. Data was statistically significant when p<0.1.

 

Results

Both the treatment and placebo groups developed objective and patient reported evidence of neurotoxicity over the course of oxaliplatin treatment, although there were no significant differences across any parameters between the two groups. However, across follow-up assessments, TNS-r score was higher in the treatment group with 8.3±2.7 compared to 4.6±3.6 (p=0.032) in the placebo group indicating greater neuropathy at 4-weeks post-chemotherapy which was sustained at 12-weeks post-treatment (p=0.089). Similarly, the FACT-GOG NTX score showed worsening symptoms in the treatment group with 37.4±10.2 compared to 43.3±7.4 (p=0.012) in the placebo group at 4-weeks post-treatment.

 

Conclusion

This study is the first to provide an objective clinical investigation of riluzole in oxaliplatin-induced peripheral neuropathy employing both functional and neurophysiological measures. Although the recruitment target was not reached, the results do not show any benefit of riluzole in minimising neuropathy development.